Adrenoleukodystrophy is a rare hereditary neurometabolic disease. It affects 1 in every 17,000 inhabitants, mainly men, although some female carriers may suffer milder forms of the disease. It is caused by mutations in the ABCD1 gene and damages myelin, the membrane that insulates nerve cells in the brain.

There are different variants of the disease, with various levels of severity, which can affect different members of the same family. The most serious is infantile cerebral adrenoleukodystrophy, which is a degenerative lethal disease affecting children 5 to 10 years old. The milder variants are chronic. The molecular mechanisms that regulate brain inflammation and give rise to more or less severe forms of the disease are not fully understood, claiming for more intense research efforts.

In this project, the research team will try to elucidate the molecular bases of the disease and identify the factors that lead to the loss of myelin. To do so, they will use cutting-edge technologies and develop new models of the disease using cells cultured in the lab from patients with the two variants. This may help identify molecular mechanisms and potential biomarkers for the disease. The results obtained in the project will allow for improved understanding and management of the disease, pave the way for future clinical trials and facilitate the implementation of neonatal screening for early diagnosis.

The laboratory of Dr. Manel Esteller, ICREA professor, head of the Cancer Epigenetics group at the Josep Carreras Leukemia Research Institute and chairman at the University of Barcelona, ​​will contribute to the project with its extensive experience in the molecular analysis of diseases, especially cancer, and mastery of cutting-edge methodologies such as spatial transcriptomics, epigenetic modifications and single-cell studies.

The grants from the CaixaResearch program, which are already in their seventh edition, are highly competitive. In this call for proposals, in collaboration with the Fundação para a Ciência e a Tecnologia, of the Ministry of Science, Technology and Higher Education of Portugal, 29 projects have been selected from a total of 580 proposals, representing a commitment to excellence and high-level, high-impact research.